Jacob Dayton Contributing Writer
In the renowned scientific journal, Nature, Grunwald et al. published their results earlier this month for the world’s first successful CRISPR/Cas9 manipulated inheritance in mice. Specifically, this means that unlike normal Mendelian inheritance in sexual organisms, where an individual inherits a single allele from their mother and one from their father, these scientists were able to ensure that as many as 86 percent of offspring inherited a specific allele from the female parent.
To test their method in mice, scientists engineered a “CopyCat” DNA element that could be inserted into the mouse Tyrosinase gene; Tyrosinase encodes an enzyme involved in pigmentation and fur color. When this CopyCat element disrupts both copies of the gene in a mouse, the mouse’s fur will be white (no pigment) instead of black. Employing the CRISPR/Cas9 gene-editing tool, Grunwald et al. were able to edit female mouse eggs to ensure that as many as 86 percent of the fertilized eggs contained the proper CopyCat/Tyrosinase- allele. Upon fertilization by male sperm, the success of the inheritance-manipulation step could be analyzed by the resultant frequency of white-coated mice.
The importance of this new technique will immediately revolutionize biomedical research of human diseases in mice. Currently, studying human genetic diseases in mouse models is exceedingly difficult, as the process involves engineering mouse strains and then breeding individuals harboring mutations similar to the human-disorder states. With the advent of inheritance manipulation, scientists will now be able to rapidly breed sufficient mice for experiments.
Furthermore, this work will likely open the door for future ethical discussions on these applications in human germ cells. For example, if a human is heterozygous for a DNA mutation that increases the probability of acquiring breast cancer by 60 percent, manipulated inheritance could substantially decrease the likelihood that a child will receive that allele. More notably, this technology could ensure that the frequency of genetic disorders, such as Huntington’s disease, decrease in the human population. These important and potentially ethically ambiguous situations will require substantial discussion in the future.